Early predictors of success of non-invasive positive pressure ventilation in hypercapnic respiratory failure

Background

Non-invasive positive pressure ventilation (NIPPV) has emerged as a significant advancement in the management of acute hypercapnic respiratory failure.

Method

Patients with hypercapnic respiratory failure requiring ventilation therapy (respiratory rate [RR] of > 30 breaths per minutes, PaCO2 > 55 mmHg and arterial pH < 7.35) were included in the study. Baseline clinical parameters and arterial blood gas (ABG) were recorded before initiating NIPPV. Clinical parameters including heart rate (HR), RR, oxygen saturation and ABG were revaluated at 1, 4, and 24 hours after initiation of NIPPV. Change in these parameters and need for intubation was evaluated.

Results

Of the 100 patients, 76 (76%) showed improvement in clinical parameters and ABG. There was improvement in HR and RR, pH, and PCO2 within the first hour in the success group and these parameters continued to improve even after four and 24 hours of NIPPV treatment. Out of 24 (24%) patients who failed to respond, 13 (54%) needed endotracheal intubation within one hour. The failure group had higher baseline HR than the success group.

Conclusion

Improvement in HR, RR, pH, and PCO2 one hour after putting the patient on NIPPV predicts success of non-invasive positive pressure ventilation in hypercapnic respiratory failure.     

Article not available electronically: Neurocognitive impairment in alcohol-dependence syndrome cases and its response to treatment

Background

A sizeable portion of psychiatric ward beds in military hospitals is occupied by patients with psychoactive substance abuse and especially by alcohol-dependence syndrome (ADS) cases. Though there have been significant advances in the diagnosis and management of these cases, not much of work has been done in our set up for the evaluation of their cognitive impairment and its response to treatment.

Methods

Neuropsychological evaluation of 100 cases of freshly diagnosed ADS was done by using postgraduate battery of brain dysfunction (PGI-BBD). The findings were compared with controls. They were detoxified, treated and after four weeks were re-evaluated and the findings were analysed.

Results

There was significant impairment in all parameters of cognition. All of them showed improvement with treatment but after four weeks, the impairment persisted to significant level in some parameters.

Conclusion

Alcohol-dependence syndrome cases have significant cognitive impairment but improve with detoxification, multivitamin supplement and abstinence. This aspect has to be kept in mind while deploying them in sensitive appointments.     

The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1

Although the dominant approach to drug development is the design of compounds selective for a given target, compounds targeting more than one biological process may have superior efficacy, or alternatively a better safety profile than standard selective compounds. Here, this possibility has been explored with respect to the endocannabinoid system and pain. Compounds inhibiting the enzyme fatty acid amide hydrolase (FAAH), by increasing local endocannabinoid tone, produce potentially useful effects in models of inflammatory and possibly neuropathic pain. Local increases in levels of the endocannabinoid anandamide potentiate the actions of cyclooxygenase inhibitors, raising the possibility that compounds inhibiting both FAAH and cyclooxygenase can be as effective as non-steroidal anti-inflammatory drugs but with a reduced cyclooxygenase inhibitory ‘load’. An ibuprofen analogue active in models of visceral pain and with FAAH and cyclooxygenase inhibitory properties has been identified. Another approach, built in to the experimental analgesic compound N-arachidonoylserotonin, is the combination of FAAH inhibitory and transient receptor potential vanilloid type 1 antagonist properties. Although finding the right balance of actions upon the two targets is a key to success, it is hoped that dual-action compounds of the types illustrated in this review will prove to be useful analgesic drugs.     

Chitinase 3-Like-1 Expression in Colonic Epithelial Cells as a Potentially Novel Marker for Colitis-Associated Neoplasia

Chitinase 3-like-1 (CHI3L1/YKL-40) is a protein secreted from restricted cell types including colonic epithelial cells (CECs) and macrophages. CHI3L1 is an inflammation-associated molecule, and its expression is enhanced in persons with colitis and colon cancer. The biological function of CHI3L1 on CECs is unclear. In this study, we investigated the role of CHI3L1 on CECs during the development of colitis-associated neoplasia. We analyzed colonic samples obtained from healthy persons and from persons with ulcerative colitis with or without premalignant or malignant changes. DNA microarray and RT-PCR analyses significantly increased CHI3L1 expression in non-dysplastic mucosa from patients with inflammatory bowel disease (IBD) who had dysplasia/adenocarcinoma compared with that in healthy persons and in patients with IBD who did not have dysplasia. As determined by IHC, CHI3L1 was expressed in specific cell types in the crypts of colonic biopsies obtained from patients with ulcerative colitis who have remote dysplasia. Purified CHI3L1 efficiently activated the NF-κB signaling pathway and enhanced the secretion of IL-8 and TNF-α in SW480 human colon cancer cells. In addition, colon cancer cell proliferation and migration were significantly promoted in response to CHI3L1 in these cells. In summary, CHI3L1 may contribute to the proliferation, migration, and neoplastic progression of CECs under inflammatory conditions and could be a useful biomarker for neoplastic changes in patients with IBD.Chitinase 3-like-1 (CHI3L1, also known as YKL-40 or HC-gp39) is classified in the glycosyl hydrolases 18 family based on the structural similarity with other chitinases.^1,2 However, functionally, CHI3L1 lacks enzymatic activity and belongs to the family of chi-lectins (chitinase-like lectins) that includes Ym-1³ and stabilin-1-interacting chitinase-like protein.⁴ CHI3L1 is a 40 kDa protein and is produced by restricted cell types, including colonic epithelial cells (CECs) and macrophages.^5–7 CHI3L1 can be detected in the Golgi apparatus and the endoplasmic reticulum,⁸ but its major sites of action seems to be extracellular as a secreted protein.⁹ The secreted form of CHI3L1 has growth-stimulating effects in connective tissue cells, including synoviocytes and chondrocytes.¹⁰ In addition, CHI3L1 shows dose-dependent growth-stimulating effects in human fibroblasts and shows similar and synergistic effects with well-characterized mitogen, insulin-like growth factor 1 (IGF-1).¹¹ However, the exact biological function of CHI3L1 in CECs remains uncertain.It is well documented that elevated levels of CHI3L1 can be detected in the sera of persons with rheumatoid arthritis, bronchial asthma, or inflammatory bowel disease (IBD).^12–15 Serum CHI3L1 is significantly increased in active but not quiescent IBD.^5,9,15 In agreement with this observation, approximately 64% of persons with Crohn''s disease (CD) who have extra-intestinal manifestations such as erythema nodosum and fistulas showed significantly increased serum levels of CHI3L1.^15,16 In addition, patients with CD who had stenotic disease had higher serum CHI3L1 than did patients with non-stenotic disease.¹⁷ Of note, the colonic CHI3L1 mRNA level was increased in persons with active ulcerative colitis (UC) and CD but was in the normal range in persons with quiescent UC and the uninvolved regions of CD.⁵ In addition, CHI3L1 serum concentrations seem to be not only highly up-regulated in persons with active CD and UC but also correlated with poor prognosis of solid tumors, including breast cancer and colon cancer.⁹Patients with chronic IBD have an increased risk of developing colitis-associated cancer, which increases by 0.5% to 1% annually after 10 years of chronic inflammation.¹⁸ A growing amount of evidence indicates that various soluble factors produced by epithelial cells and immune cells play a pathogenic role in the carcinogenic change of CECs.^19,20 CHI3L1 seems to be one of the soluble factors that play a pivotal role in protecting cancer cells from undergoing apoptosis, as well as promoting tissue remodeling by interacting with the extracellular matrix and by stimulating angiogenesis.²¹ However, little is know about the role of CHI3L1 in IBD-associated colon cancer.In this study we show that CHI3L1 expression in CECs is significantly and specifically increased in non-dysplastic mucosa of patients with UC who have dysplasia that is away from the non-dysplastic mucosa (remote dysplasia) as well as colorectal adenocarcinoma; we also show that it may be a reliable biological marker of neoplasia in high-risk individuals. In addition, we demonstrate a new mechanism by which CHI3L1 may contribute to IBD-associated neoplasia through a growth-stimulating effect on enhancing the production of NF-κB–induced IL-8 and tumor necrosis factor (TNF)-α, which presumably are associated with chronic inflammation-mediated malignant transformation in CECs.     

Monosegmental fixation for the treatment of fractures of the thoracolumbar spine

Background:

A short vertebral arthrodesis has been one of the objectives of the surgical treatment of fractures of the thoracolumbar spine. We present here clinical, functional and radiographic outcome obtained after monosegmental fixation (single posterior or combined anterior and posterior) of specific types of unstable thoracolumbar fractures.

Materials and Methods:

Twenty four patients with fractures of the thoracolumbar spine submitted to monosegmental surgical treatment (Group I - 18 single posterior monosegmental fixations and Group II - 6 combined anterior and posterior fixations) were retrospectively evaluated according to clinical, radiographic and functional parameters. The indication for surgery was instability or neurological deficit. All the procedures were indicated and performed by the senior surgeon (Helton LA Defino).

Results:

The patients from group I were followed-up from 2 to 12 years (mean: 6.65±2.96). The clinical, functional and radiographic results show that a single posterior monosegmental fixation is adequate and a satisfactory procedure to be used in specific types of thoracolumbar spine fractures, The patients from group II were followed-up from 9 to 15 years (mean: 13 ± 2,09 years). On group II the results of clinical evaluation showed moderate indices of residual pain and of satisfaction with the final result. The values obtained by functional evaluation showed that 66.6% of the patients were unable to return to their previous job and presented a moderate disability index (Oswestry = 16.6) and a significant reduction of quality of life based on the SF-36 questionnaire. Radiographic evaluation showed increased kyphosis of the fixed vertebral segment during the late postoperative period, accompanied by a reduction of the height of the intervertebral disk.

Conclusion:

It is possible to stabilize the fractures which have an anterior good load-bearing capacity by a standalone posterior monosegmental fixation. However this procedure, even with an anterior support is not suitable for fracture involving the vertebral body.     

Physical Activity and Risk of Small-for-Gestational-Age Birth Among Predominantly Puerto Rican Women

To estimate the association between multiple domains of physical activity and risk of small-for-gestational-age (SGA) birth. We utilized data from 1,040 participants in the Latina Gestational Diabetes Mellitus Study, a prospective cohort of predominantly Puerto Rican prenatal care patients in Massachusetts. Physical activity was assessed by bilingual interviewers using a modified version of the Kaiser physical activity survey in early (mean = 15 weeks) and mid pregnancy (mean = 28 weeks). Physical activity (i.e., sports/exercise, household, occupational, and active living) in pre, early and mid pregnancy was categorized in quartiles. SGA was classified as <10th percentile of birth weight for gestational age. Pre- and early-pregnancy physical activity were not associated with SGA. In multivariable analyses, women with high total activity in mid-pregnancy had a decreased risk of SGA [risk ratio (RR) = 0.42; 95% confidence interval (CI) 0.21–0.82; p _trend = 0.003] as compared to those with low total activity. Findings were similar for high household activity (RR = 0.69; 95% CI = 0.34–1.40; p _trend = 0.26), active living (RR = 0.63; 95% CI = 0.35–1.13; p _trend = 0.04), and occupational activity (RR = 0.79, 95% CI = 0.47–1.34; p _trend = 0.26). High levels of sports/exercise were associated with an increased SGA risk without a significant dose–response association (RR = 2.14, 95% CI 1.04–4.39; p _trend = 0.33). Results extend prior studies of physical activity and SGA to the Hispanic population.